The following includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art, or relevant, to the presently described or claimed inventions, or that any publication or document that is specifically or implicitly referenced is prior art.
The use of laser light to measure the speed of moving particles, particularly in gases, extends back almost to the invention of the laser. Light scattered back to a detector from a moving particle suffers a Doppler shift equal to the rate of change of the phase path between the source of light and the detector. For example, it has been shown that when examined using minute detector apertures, laser light scattered from motionless skin is Doppler shifted due to the presence of moving blood particles in the dermal layers of the body. Most of the light is returned from essentially immobile scatterers in the tissue, but a portion is returned by a multiple scatter process that involves the immobile scatterers plus scattering by one or more blood particles that flow in the network of looping capillaries within 1-2 mm of the skin surface.
The multiple scatterers complicate the analysis required to quantify such measurements in physiologically useful ways. However, it was found by Bonner and Nossall (Applied Optics 20:2097-2107 (1981)) that the tissue perfusion was given by the first moment of the power spectrum of the Doppler signals, and tissue perfusion can be expressed as the product of the flow velocity and the number of moving scatterers.
Laser Doppler imaging is a current optical technique that is used to evaluate blood flow changes. The output of the instrument is a two-dimensional (2D) flow-related (perfusion, speed, concentration) map over an area of up to 50×50 cm2. The technique is non-invasive because it involves no physical contact. However, present commercial laser Doppler imagers do not completely fulfill all requirements imposed on them by clinical applications. They are slow, special skills are required to use them, and the interpretation of the obtained results is not always objective. Another problem with the Doppler method is that perfusion can only be measured at one site at a time. Mapping perfusion over an area is time consuming and does not take into account any rapid perfusion changes. With regard to the evaluation of perfusion or blood flow in a subject, for example in the skin of a subject, yet another issue with Doppler imaging is the fact that the subject, e.g., the skin or a body part under evaluation, must remain motionless. Thus, commercial laser Doppler imagers and the technique itself are mainly used in medical research projects but not often in clinical practice, despite the tremendous potential of laser Doppler imaging in the medical field. Currently, the two main optical techniques for in vivo monitoring of blood flow are laser Doppler flowmetry and laser speckle contrast imaging.
A speckle pattern is a random intensity pattern produced by the mutual interference of a set of wavefronts. When a surface is illuminated by a light wave, according to diffraction theory, each point on an illuminated surface acts as a source of secondary spherical waves. The light at any point in the scattered light field is made up of waves that have been scattered from each point on the illuminated surface. If the surface is rough enough to create pathlength differences exceeding one wavelength, giving rise to phase changes greater than 2π, the amplitude, and hence the intensity, of the resultant light varies randomly. If light of low coherence (i.e., made up of many wavelengths) is used, a speckle pattern will not normally be observed, because the speckle patterns produced by individual wavelengths have different dimensions and will normally average one another out. This phenomenon has been investigated by scientists for many years, but speckles have come into prominence since the invention of the laser and there are a variety of applications. A familiar example is the random pattern created when a laser beam is scattered off a rough surface. The speckle effect is a result of the interference of many waves having different phases, which add together to give a resultant wave whose amplitude, and therefore intensity, varies randomly. If each wave is modeled by a vector, then it can be seen that if a number of vectors with random angles are added together, the length of the resulting vector can be anything from zero to the sum of the individual vector lengths.
Laser speckle patterns are produced by illuminating the object under test with coherent light. Speckle is the grainy appearance produced by interference between path lengths which differ randomly due to microscopic surface roughness, and may be far field speckle or image speckle. Far field speckle describes the speckled nature of the illumination at some distance from a laser spot shone on a surface, and image speckle describes the speckled appearance of an object illuminated with an expanded laser beam, as imaged by some optical system such as a camera or human eye. Laser speckle contrast imaging uses the image speckle effect, in which the pixels in an image of a uniform surface show intensities in a distribution from black to white. As the object under test moves the speckle pattern translates or changes; at any particular point, the measured intensity fluctuates with object movement.
In a system of perfusion estimation, laser speckle is used to produce full field images of relative motion. Equivalent to the Doppler shift seen at a point, the laser speckle pattern “twinkles” in space because of the light scattered by the moving blood particles when the target is living skin. The greater the rate of twinkling, the more the speckle becomes blurred in an image recorded over a finite time. This twinkling is sometimes termed “biospeckle,” and the blurring is conventionally quantified by a contrast parameter K, where K is the ratio of the standard deviation of the light intensity to the mean intensity i.e.
  K  =            σ      s              I      _      where the subscript s denotes spatial variation.
Speckle images of living biological tissues such as skin show a rapidly changing speckle pattern, in contrast to the static speckle pattern produced by a stationary non-living object. This biospeckle effect is due to the scatter from moving cells, such as red cells in flowing blood, relative to the fixed scatterers as such the tissue. The spectrum of this fluctuation is determined by the number and speed of the moving particles.
The fluctuation rate can be measured indirectly by calculating the contrast over small areas of a speckle image taken at some appropriate finite exposure: if the fluctuation period at a certain point in the image is short enough compared to the exposure time, the speckle fluctuations will be blurred. Low contrast areas of the image indicate a high fluctuation rate, hence high rates of cell movement. This phenomenon has been used to produce various similar laser speckle imaging systems. These systems are sensitive to relative tissue perfusion, a measure of blood flow proportional to the product of the speed and concentration in tissue of flowing blood cells. However, the challenge for laser speckle techniques is determining a quantitative measurement of perfusion from the speckle statistics. Notwithstanding opporunities around real-time visualization of speckle contrast, real-time quantitative analysis has hitherto been lacking
Thus, perfusion—blood flow in tissues—can be measured using laser Doppler techniques or laser speckle contrast imaging. Laser Doppler and laser speckle methods essentially measure the same physical effect, though they use different measurement techniques and interpretations. Doppler methods measure perfusion from the first moment of the power spectrum of the fluctuations in light returned from a small area of the tissue (Briers, J. D., “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging” Physiological Measurement 22:R35-R66 (2001)), which has been shown to be linearly related to blood flow by calculation and in vitro experiments (Bonner and Nossal, “Model for laser Doppler measurements of blood flow in tissue” Applied Optics 20:2097-2107 (1981) and modelling (Jentink, et al., “Monte Carlo simulations of laser Doppler blood flow measurements in tissue” Applied Optics 29:2371-2381 (1990)). This was initially a single point measurement, using a probe to measure the spectrum returned from a small volume of tissue illuminated by laser light, though an image of an area of tissue can be produced by scanning the measurement point. Laser speckle perfusion measurements, on the other hand, use the spatial statistics of the fluctuating laser speckle pattern (biospeckle) recorded by a camera at a finite exposure to generate a map of relative perfusion. Laser speckle perfusion is an area measurement by nature, producing an image with every exposure, by comparison with laser Doppler images produced by scanning. As noted above, a current challenge for laser speckle techniques is determining a quantitative measurement of perfusion from the speckle statistics.
Thus, it will be appreciated that laser Doppler and laser speckle imaging are two optical non-invasive techniques that are used to obtain 2D maps of blood flow in biological tissues, and each of these existing techniques has benefits and drawbacks for measuring the blood flow. Laser speckle contrast imaging can be seen as a real-time imaging technique, but the interpretation of its response to changes in flow parameters such as speed and concentration is problematic. In contrast, laser Doppler imaging has clearer biological interpretation but it is not a real-time technique.
In one embodiment, a new laser speckle imaging system takes speckle contrast measurements over multiple exposure times and uses temporal autocorrelation information derived from speckle contrast measurements to provide spectral information and a perfusion index that is precisely equivalent to that produced in laser Doppler methods.
In another embodiment, numerically constructed autocorrelation data are approximated by mathematical functions with an adjustable parameter τc. The speckle contrast information is determined from each of the plurality of images and a plurality of contrast images are formed therefrom. From the plurality of contrast images, one or more parameters of a temporal autocorrelation function representative of tissue speckle are derived. A perfusion value of a fluid moving through the medium is determined from the one or more parameters.
The various embodiments of the invention described and claimed herein thus overcome the drawbacks of laser speckle imaging and provide particulate flow and velocity images in real time over a scanned area that are equivalent to laser Doppler images taken at a static single point.